乳腺癌中ERα、PR的表达与预后关系及其影响阳性率的相关因素

目的分析乳腺癌中ERα、PR的阳性率与预后的关系,探讨影响ERα、PR阳性率的相关因素。方法采用免疫组化En Vision法检测662例乳腺癌组织中ERα、PR的表达,按不同阳性率分组,Kaplan-Meier法分析预后。选择其中的80例采用两种克隆号ERα(SP1、6F11)染色并由一位高年资医师判读,以分析不同克隆号对阳性率的影响;选择其中的214例ERα(SP1)由三位不同年资医师采用Allred score、H score两种判读系统分别判读,以观察不同判读系统及医师经验对阳性率的影响。一致性采用Kappa检验。结果生存分析显示,ERα、PR低阳性组无病生存率(disease-free survival,DFS)、总生存率(overall survival,OS)均优于阴性组(DFS:P=0.021、0.003)、(OS:P=0.019、0.003),ERα、PR高阳性组DFS、OS均优于低阳性组(DFS:P=0.011、0.002)、(OS:P=0.012、0.005)。浸润性癌非特指型、浸润性小叶癌、导管原位癌ERα阳性率分别为59.5%、78.9%、63.6%,差异有统计学意义(P=0.002),PR阳性率分别为56.3%、68.9%、59.1%,差异无统计学意义(P=0.079)。不同组织学分级的浸润性癌非特指型ERα、PR阳性率差异有统计学意义(P均0.001)。不同核级导管原位癌ERα、PR阳性率差异有统计学意义(P均0.05)。克隆号SP1阳性细胞百分率、染色强度均优于6F11;判读系统H score重复性略优于Allred score;高年资医师间阳性细胞百分率、染色强度判读重复性好(κ=0.850,κ=0.824),而高年资和低年资医师之间重复性均较差(0.4κ0.75);阳性细胞百分率估计法与计数法重复性较差(κ=0.726)。结论 ERα、PR不同阳性细胞百分率与患者预后密切相关,影响ERα、PR阳性率的因素包括病理类型、组织学分级、核分级、抗体的选择、判读系统及判读医师间的差异等。     

外源性已烯雌酚对新生雌性BALB/c小鼠脾内细胞雌激素受体表达的影响

目的了解新生期注射己烯雌酚（DES）后雌性BALB／c小鼠脾内细胞雌激素受体表达的动态变化。方法雌性BALB／c小鼠在生后24h内,颈背部皮下注射DES,每隔24h注射1次,共连续注射5次。对照组平行注射等量无菌豆油。分别在生后7、14、21、35和49d将小鼠处死,取其脾组织进行常规石蜡包埋、切片及雌激素受体（ER）的免疫组织化学检测。结果对照组与DES组雌性小鼠脾内均可见ER阳性细胞,ER阳性细胞主要是淋巴细胞,其阳性强度在两组均呈增龄性变化;DES组小鼠脾内ER阳性细胞强度高于对照组,两组之间存在显著性差异。结论雌性BALB／c小鼠脾内存在表达ER的细胞,其表达水平随着年龄的增加而有所增加;新生期接触DES可以导致雌性BALB／c小鼠脾ER阳性细胞的增加,并可至少持续到成年期。     

垂体嫌色细胞瘤雌激素受体和催乳素的表达及其相互关系

本文应用许良中改良的PAP法检测雌激素受体(ER),应用常规PAP法检测催乳素(PRL)。58例垂体嫌色腺瘤ER阳性40例(63.9%,Ⅰ级20例,Ⅱ级16例和Ⅲ级3例)和PRL阳性42例(72.4%,Ⅰ级6例,Ⅱ级21例和Ⅲ级15例);18例ER阴性病例中PRL阴性10例,40例ER阳性病例中PRL阳性34例,ER阳性率和PRL阳性率存在密切关系(P<0.005),另外,ER半定量分级与PRL半定量分级也存在密切关系(P<     

免疫组织化学标记结果的判断方法

免疫组织化学在肿瘤病理诊断和鉴别诊断中广泛应用 ,但对其标记结果的认定判断尚不一致 :同一染色切片 ,有的说是阳性 ,也有的说是阴性 ;或同一阳性结果 ,可有不同程度的判断结果 ;在阳性程度划分上也分歧较大 ,而且因判断标准不同 ,得出的结果则相反。这是目前免疫组织化学检测中十分重要的问题。目前对免疫组化染色阳性标准尚不一致 ,有的以阳性细胞数目计算 ,有的以染色强度判断 ;具体在阳性细胞百分率和阳性程度认同上也存在的差异 ,给临床医师对其结果的理解带来了困难。肿瘤病理诊断以 ( - )、( )表示免疫组化结果 ,临床医师不难理…     

肥大细胞表面抗原-1高灵敏度定量分析法的建立

目的建立肥大细胞表面抗原-1(MASA-1)的高灵敏度定量分析方法。方法首先制备抗人MASA-1的单克隆抗体,然后结合先前制备的多克隆抗体,通过优化包被浓度、温度和反应时间等条件,建立夹心酶联免疫定量方法。结果成功制备了特异性高的小鼠抗人MASA-1的单克隆抗体;夹心ELISA法的检测灵敏度可达0.5 ng/ml。利用该法测出各种呼吸系统疾病病人的肺清洗液中的MASA-1含量为0～130 ng/ml。MASA-1的浓度与甲苯胺蓝染色阳性细胞数之间不存在相关关系,但与MASA-1染色阳性细胞数之间呈显著正相关关系。结论相对于MASA-1细胞染色法,本研究开发的酶联免疫法具有快速、准确及能同时分析大量样品的优点,有助于肥大细胞的实验室研究和临床检测。     

米非司酮对人脐静脉平滑肌雌、孕激素受体的影响

目的:探讨米非司酮对脐静脉平滑肌组织雌、孕激素受体(ER、PR)的影响。方法:将有终止妊娠指征的中孕病例随机分为米非司酮组(n=10)与对照组(n=5)。米非司酮组在水囊引产术前6h服用米非司酮150mg,对照组只行水囊引产术。胎盘娩出后,即取脐带组织制备样品。应用免疫组化法检测脐静脉平滑肌组织的ER与PR,并结合图像分析技术进行定量分析,用阳性单位(PU)值表示免疫组化阳性反应程度。结果:ER、PR的阳性染色部位为脐静脉平滑肌细胞核。米非司酮组脐静脉平滑肌ER含量(13.87±1.42)明显多于对照组(10.31±0.76),PR含量(3.84±0.48)则明显少于对照组(6.55±0.36),P值均小于0.01。结论:米非司酮可减少脐静脉平滑肌PR含量,因而造成的血管收缩可能危及胎儿的成长和生存。     

子宫内膜癌组织中内分泌分化细胞的生物学特性及意义

观察子宫内膜癌组织中内分泌分化细胞的增殖与凋亡状况、雌激素受体(ER)与孕激素受体(PR)表达,探讨其生物学及临床意义。手术切除或活检的子宫内膜癌标本50例。采用嗜铬素A(CgA)作为内分泌分化的标记,进行CgA／PCNA及CgA/TUNEL双重染色,观察内分泌分化细胞的增殖与凋亡状况;并进行CgA与生存素(Survivin)双重免疫组化染色,探讨生存素与内分泌分化细胞凋亡的关系。通过CgA/ER及CgA/PR双重免疫组化染色观察内分泌分化细胞的ER、PR表达。结果显示CgA阳性细胞呈PCNA及TUNEL染色阴性。CgA阳性细胞多表达Survivin。CgA阳性细胞密集的区域ER或PR减少明显。大多数CgA阳性细胞不表达ER或PR。结果提示子宫内膜癌组织的内分泌分化细胞属暂不增殖细胞群,亦极少发生凋亡,是较稳定的细胞群。内分泌分化细胞高表达Survivin可能是其逃避凋亡的分子学基础。子宫内膜癌组织的内分泌分化与ER和PR的减少有关。     

大鼠下颌下腺卵泡刺激素受体、雌激素α受体的分布及与促性腺激素释放激素受体的共存

目的 研究卵泡刺激素受体( FSHR)和雌激素α受体(ERα)在大鼠下颌下腺中的定位、分布及与促性腺激素释放激素受体( GnRHR)共存.方法采用免疫组织化学定位和邻片免疫组织化学共定位方法.结果大鼠下颌下腺浆液性腺泡及各级导管的上皮细胞均呈FSHR和ERα免疫反应阳性;在下颌下腺GnRHR免疫反应阳性细胞中观察到了F...     

Preferences selection of immunohistochemistry semiquantitative analysis by Image Pro Plus image analysis system

目的:应用Image Pro Plus (IPP)图像分析软件测算阳性细胞面积(area)、平均光密度值、积分光密度值,研究面积参数选择、阳性结果选色方式对免疫组织化学结果的影响,以期获得IPP图像分析免疫组织化学的标准化结果.方法:采用人工计数法将矽肺免疫组织化学结果分为低表达、中表达、高表达3组.应用IPP软件,面积选择参数分为过滤10、30、50、100以下的阳性显色；采用吸管取色、RGB、HIS 3种选择阳性显色的方法；编写宏文件,计算各组阳性细胞面积、平均光密度值(MD)、移分光密度值(IOD)的均值和总和,并与人工计数法测算结果进行比较.结果:在滤过面积10～100范围内,面积参数对各组阳性细胞面积总和、IOD总和统计结果无影响,与人工计数法结果一致；采用HIS选色测算的面积总和、IOD总和与人工计数法结果一致.结论:IPP图像分析能够简易、快速地进行免疫组织化学结果的半定量分析,面积参数在一定范围内对测算结果无影响,HIS选色方式可能较吸管显色和RGB选色方式好,而IOD总和是比较可靠、稳定的半定量指标.     

胰腺良恶性病变中性激素受体的表达及意义

应用许良中改良PAP法检测43例胰腺癌和20例胰腺良性病变组织中雌激素受体(ER)和孕酮受体(PR)的表达,探讨其意义。43例胰腺癌ER阳性29例(67.4%)和PR阳性22例(51.2%),15例胰腺慢性炎症仅1例导管上皮ER和PR阳性,5例胰腺真性囊肿上皮1例ER和PR阳性;胰腺高分化腺癌ER和PR阳性率分别为     

Schizophrenia in a North Swedish geographical isolate, 1900–1977. Epidemiology, genetics and biochemistry

Over 200 schizophrenic patients belonging to three major and interrelated pedigree complexes have been investigated over the past 30 years in a North Swedish geographically isolated population, presently numbering about 6,000. An intensive investigation of a number of biochemical correlates and genetic markers in a few selected families belonging to one of the major pedigrees has indicated new strategies for the current research program.
Schizophrenia, as defined operationally, is significantly associated with decreased activities of two enzymes (1) blood platelet monoamine oxidase, (2) plasma dopamine-β-hydroxylase, and (3) with the genetic marker Gc² (group specific antigen). Both enzymes are subject to genetic variation. A positive score for linkage between schizophrenia and low plasma DBH activity has been calculated, but, so far, available data are insufficient for discrimination between linkage and partial contribution of genetically controlled low plasma DBH to the pathogenesis of the disease. Alternatively, both mechanisms could be involved.
As a model for continued research, schizophrenia is explained as based on a double dominant-recessive genotype (Aabb), representing a vulnerability which in about 50 % of cases develops into clinical schizophrenia. It is suggested that the dominant mutation (A) operates on or affects MAO activity, and that the recessive genotype (bb) is instrumental in low variates of DBH activity and very likely such variates within the normal range of physiological variation. Moreover, it is suggested that the combined effects of MAO- and DBH-reduced efficiency on the metabolism of e.g. dopamine could be an essential pathogenic mechanism for the schizophrenic illness which is segregating in this population.     

Renal dysplasia and asplenia in two sibs

A family is reported in which two sibs, one male and the other female, both died within 24 hours of birth with enlarged polycystic kidneys. Postmortem histology in the second child showed gross renal dysplasia. In both children the pancreas was enlarged, nodular and cystic but the liver appeared macroscopically normal. In the second child, histological examination confirmed pancreatic fibrosis with cystic dilation of ducts, but showed portal fibrosis with bile duct proliferation in the liver.
This combination of findings is very reminiscent of those in a girl and her brother reported by Ivemark et al. (1959). The children reported here also showed absence or hypoplasia of the spleen, cardiac anomalies and other features of the Ivemark syndrome (Ivemark 1955), a quite different, usually sporadic, congenital disorder. It is suggested that the children described here have a distinct lethal congenital disorder, probably inherited in an autosomal recessive manner.     

The dominant diseases of modernized societies as omega-3 essential fatty acid deficiency syndrome: Substrate beriberi

About 1900, modern food selection and processing caused widespread $\text{epidemics}$ of the B vitamin deficiency diseases of beriberi and pellagra which, for genetic reasons, often expressed as different diseases ranging from bowel and heart disease to dermatoses and psychoses. But the B vitamins merely help convert essential fatty acids (EFA) into the prostaglandin (PG) tissue regulators and it now turns out that, through hydrogenation, milling and selection of w3-poor southern foods, we have also been systematically depleting, by as much as 90%, a newly discovered trace Nordic EFA (w3) of special importance to primates and sole precursor of the PG3(4) series, even as a concurrent fiber deficiency increases body demand for EFA. Since substrate EFA is processed by many B vitamin catalysts, an EFA deficiency will mimic a $\text{panh}$ypovitaminosis B, i.e., a mixture of $\text{substrate}$ beriberi and $\text{substrate}$ pellagra resembling vitamin beriberi and pellagra but exhibiting as even more diverse $\text{endemic}$ disease. This would consitute a second stage of the Modern Malnutrition and explain why some workers now hold the dominant diseases of modermized societies to be new, nutritionally based, pellagraform yet lipid-related and to range, once again, from heart disease to psychosis. It is an assumption that our dominant diseases are unrelated to each other or are merely revealed by our diagnostic acumen and therapeutic success; and that hydrogenating millions of tons of food oils annually, to destroy the rancidity producing w3-EFA, is safe for $\text{primates}$. Extensive beriberiform disease is reported here in 32 typical cases taken from medical practice which responds strikingly to linseed oil supplements (60% w3-EFA) in confirmation of identical results in Capuchins.     

'Very sore nights and days': the child's experience of illness in early modern England, c.1580-1720

Sick children were ubiquitous in early modern England, and yet they have received very little attention from historians. Taking the elusive perspective of the child, this article explores the physical, emotional, and spiritual experience of illness in England between approximately 1580 and 1720. What was it like being ill and suffering pain? How did the young respond emotionally to the anticipation of death? It is argued that children’s experiences were characterised by profound ambivalence: illness could be terrifying and distressing, but also a source of emotional and spiritual fulfilment and joy. This interpretation challenges the common assumption amongst medical historians that the experiences of early modern patients were utterly miserable. It also sheds light on children’s emotional feelings for their parents, a subject often overlooked in the historiography of childhood. The primary sources used in this article include diaries, autobiographies, letters, the biographies of pious children, printed possession cases, doctors’ casebooks, and theological treatises concerning the afterlife.     

Guidelines for the Validation and Use of Immunoassays for Determination of Introduced Proteins in Biotechnology Enhanced Crops and Derived Food Ingredients

Recent advancements in agricultural biotechnology have created a need for analytical techniques to determine introduced proteins in crops enhanced through modern biotechnology techniques. These proteins are expressed in plant tissues and may be present in food ingredients. Immunoassays are ideally suited for protein detection and may be used as both quantitative and threshold methods. Microplate ELISA and lateral flow devices are two of the most commonly used immunoassay formats for agricultural biotechnology applications. This paper provides general background information and a discussion of criteria for the validation and application of immunochemical methods to the analysis of proteins introduced into plants and food ingredients using biotechnology methods. It is the result of a collaborative effort of members of the Analytical Environmental Immunochemical Consortium. This collaborative effort represents the combined expertise of several organizations to reach consensus on establishing guidelines for the validation and use of immunoassays. Further, the paper offers developers and users a consistent approach to adopting the technology as well as aid in producing accurate and meaningful results.     

Ultracryotomy: development and application (with examples from the yeast cytology) (author's transl)

The preparation steps usually necessary for obtaining ultrathin frozen sections of biological material (chemical prefixation, enclosing, cryoprotective treatment, freezing, sectioning, and post-staining the sections for transmission electron microscopy) are submitted to a critical analysis. The application of cryo-ultramicrotomy, in particularly for cytochemical purposes, is reviewed. Fundamental considerations of chemical prefixation and poststaining are supported by examples from yeast cytology. Furthermore, the efficiency of the cryo-ultramicrotomy (electron optical resolution of ultrastructural details) is demonstrated on yeast cells and protoplasts.     

HLA in North Colombia Chimila Amerindians

HLA-A,-B,-C,-DRB1 and -DQB1 alleles have been studied in Chimila Amerindians from Sabana de San Angel (North Colombian Coast) by using high resolution molecular typing. A frequent extended haplotype was found:HLA-A*24:02-B*51:10-C*15:02-BRB1*04:07-DQB1*03:02 (28.7%) which has also been described in Amerinndian Mayos Mexican population (Mexico, California Gulf, Pacific Ocean). Other haplotypes had already been found in Amerindians from Mexico (Pacific and Atlantic Coast), Peru (highlands and Amazon Basin), Bolivia and North USA. A geographic pattern according to HLA allele or haplotype frequencies is lacking in Amerindians, as already known. Also, five new extended haplotypes were found in Chimila Amerindians. Their HLA-A*24:02 high frequencies characteristic is shared with aboriginal populations of Taiwan; also, HLA-C*01:02 high frequencies are found in New Zealand Maoris, New Caledonians and Kimberly Aborigines from Australia. Finally, this study may show a model of evolutionary factors acting and rising one HLA allele frequency (-A*24:02), but not in others that belong to the same or different HLA loci.     

The case for allele‐specific recognition by the TCR

There is a sharp difference in how one views TCR structure–function–behaviour dependent on whether its recognition of major histocompatibility complex‐encoded restriction elements (R) is germline selected or somatically generated. The generally accepted or Standard model is built on the assumption that recognition of R is by the V regions of the αβ TCR, which is not driven by allele specificity, whereas the competing model posits that recognition of R is allele‐specific. The establishing of allele‐specific recognition of R by the TCR would rule out the Standard model and clear the road to a consideration of a competing construct, the Tritope model. Here, the case for allele‐specific recognition (germline selected) is detailed making it obvious that the Standard model is untenable.     

The universal muscular chamber. A basic unit of the genitourinary, cardiovascular, gastro-intestinal, skeletal, cutaneous, respiratory and other systems, endocameral hypertension; and spasm, the key to their idiopathic diseases and arthropathies

Starting with the integument, we see many organs are contractile sacs or multiples thereof, which tubes or bags constitute the major part of the entire body. Recognition of this basic unit and its characteristics sheds new light, individually and collectively, on many disorders previously considered unrelated. Muscular tears and perforations develop in the walls of these chambers, being no way peculiar to those organs, wherein, hydrochloric acid occurs. So, it is not necessary to explain the absence of excessive acid from patients who exhibit holes in the gastric, uterine, aortic, duodenal, rectal, pulmonary, retina, and other walls. Muscle, not acid is the great common factor relating idiopathic disorders in the gastrointestinal tract to each other and to similar diseases in other systems. When the units are linked together, the lesions tend to appear as arthropathies, i.e. at the joints. Rephrasing common-place observations, frees us from conventional, conceptual cul-de-sacs. An observation is only as good as its interpretation, so all possibilities must be considered, otherwise, we will remain blinded by our misconceptions.